siRNA specific to WT1 17AA(−)isoform and use thereof

Abstract

Disclosed is a polynucleotide having at least 15 contiguous bases in the base sequence of SEQ ID NO:26 and including the base sequence of SEQ ID NO:27. Also disclosed is siRNA produced based on the polynucleotide. By means of this, a cancer cell-specific molecular-targeted therapy, which successfully controls the function of WT1, can be realized.

1. An isolated polynucleotide of 15 to 49 bases in length comprising at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 that include the nucleotide sequence of SEQ ID NO:27. 
     
     
       2. A polynucleotide consisting of the nucleotide sequence of SEQ ID NO:26. 
     
     
       3. A medical composition for treating a solid tumor, the composition comprising any one of:
 (a) a double-stranded RNA consisting of 15 to 49 base pairs, 
 (b) a DNA encoding the double-stranded RNA, or 
 (c) a vector comprising the DNA; 
 wherein the double-stranded RNA can specifically inhibit expression of WT1 17AA(−) isoform without inhibiting expression of WT1 17AA(+) isoform, and wherein the double-stranded RNA comprises:
 (i) a first RNA comprising bases that are the complement of at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 that include the nucleotide sequence of SEQ ID NO:27 and 
 (ii) a second RNA complementary to the first RNA. 
 
 
     
     
       4. The medical composition according to  claim 3 , wherein DNA encoding the second RNA hybridizes under a stringent condition with a polynucleotide having at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 and including the nucleotide sequence of SEQ ID NO:27. 
     
     
       5. The medical composition according to  claim 3 , wherein the second RNA includes at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:29. 
     
     
       6. The medical composition according to  claim 3 , wherein the first RNA includes at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:30. 
     
     
       7. The medical composition according to  claim 3 , wherein the DNA encoding the double-stranded RNA includes the nucleotide sequence of SEQ ID NO:27. 
     
     
       8. The medical composition according to  claim 3 , wherein the double-stranded RNA comprises the nucleotide sequence of SEQ ID NO:29 hybridized to the nucleotide sequence of SEQ ID NO:30. 
     
     
       9. A medical kit for treating a solid tumor, the kit comprising any one of:
 (a) a double-stranded RNA consisting of 15 to 49 base pairs, 
 (b) a DNA encoding the double-stranded RNA, or 
 (c) a vector comprising the DNA; 
 wherein the double-stranded RNA can specifically inhibit expression of WT1 17AA(−) isoform without inhibiting expression of WT1 17AA(+) isoform, and wherein the double-stranded RNA comprises:
 (i) a first RNA comprising bases that are the complement of at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 that include the nucleotide sequence of SEQ ID NO:27 and 
 (ii) a second RNA complementary to the first RNA. 
 
 
     
     
       10. A method for treating a solid tumor, the method comprising:
 administering a double-stranded RNA to a cell forming the solid tumor; wherein the double-stranded RNA can specifically inhibit expression of WT1 17AA(−) isoform without inhibiting expression of WT1 17AA(+) isoform, and wherein the double-stranded RNA is composed of (i) a first RNA of 15 to 49 bases in length comprising a nucleotide sequence that is the complement of at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 that include the nucleotide sequence of SEQ ID NO:27 and (ii) a second RNA complementary to the first RNA. 
 
     
     
       11. The method according to  claim 10 , wherein the administering is carried out by transducing the target cell with a vector comprising a polynucleotide encoding the first RNA and the second RNA. 
     
     
       12. The method according to  claim 10 , wherein the double-stranded RNA is 15 to 30 base pairs in length. 
     
     
       13. The method according to  claim 11 , wherein the double-stranded RNA is 15 to 30 base pairs in length. 
     
     
       14. The polynucleotide according to  claim 1 , wherein the polynucleotide is 15 to 30 bases in length. 
     
     
       15. The medical composition according to  claim 3 , wherein the double-stranded RNA is 15 to 30 base pairs in length. 
     
     
       16. The medical kit according to  claim 9 , wherein the double-stranded RNA is 15 to 30 base pairs in length. 
     
     
       17. A double-stranded RNA of 15 to 49 base pairs in length, the double-stranded RNA comprising bases that are the complement of at least 15 contiguous bases in the nucleotide sequence of SEQ ID NO:26 that include the nucleotide sequence of SEQ ID NO:27, wherein the double-stranded RNA can specifically inhibit expression of WT1 17AA(−) isoform without inhibiting expression of WT1 17AA(+) isoform. 
     
     
       18. A method for treating a solid tumor, the method comprising
 administering the double-stranded RNA according to  claim 17  to a cell forming the solid tumor.